Recombinant AAV as a Platform for Translating the Therapeutic Potential of RNA Interference

Borel, Florie; Kay, Mark A.; Mueller, Christian

doi:10.1038/mt.2013.285

Cited by 119 publications

(102 citation statements)

References 73 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…19,20 These features make AAV vectors a successful gene therapy approach for reverting genetic dysfunctions in preclinical models, 21,22 and to date, these vectors have been tested as a tool for reverting genetic disease. However, the same rationale could be used to cause a disease, generating a model for experimental analysis, but to our knowledge, this alternative application has not been tested to date.…”

mentioning

confidence: 99%

Induction of Sustained Hypercholesterolemia by Single Adeno-Associated Virus–Mediated Gene Transfer of Mutant hPCSK9

Roche-Molina

Sanz-Rosa

Cruz

et al. 2015

ATVB

148

141

View full text Add to dashboard Cite

Objectives-Patients with mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have hypercholesterolemia and are at high risk of adverse cardiovascular events. We aimed to stably express the pathological human D374Y gain-of-function mutant form of PCSK9 (PCSK9 DY ) in adult wild-type mice to generate a hyperlipidemic and proatherogenic animal model, achieved with a single systemic injection with adeno-associated virus (AAV). Approach and Results-We constructed an AAV-based vector to support targeted transfer of the PCSK9 DY gene to liver. After injection with 3.5×10 10 viral particles, mice in the C57BL/6J, 129/SvPasCrlf, or FVB/NCrl backgrounds developed long-term hyperlipidemia with a strong increase in serum low-density lipoprotein. Macroscopic and histological analysis showed atherosclerotic lesions in the aortas of AAV-PCSK9 DY mice fed a high-fat-diet. Advanced lesions in these highfat-diet-fed mice also showed evidence of macrophage infiltration and fibrous cap formation. Hepatic AAV-PCSK9 DY infection did not result in liver damage or signs of immunologic response. We further tested the use of AAV-PCSK9DY to study potential genetic interaction with the ApoE gene. Histological analysis of ApoE −/− AAV-PCSK9 DY mice showed a synergistic response to ApoE deficiency, with aortic lesions twice as extensive in ApoE −/− AAV-PCSK9 DY-transexpressing mice as in ApoE −/− AAV-Luc controls without altering serum cholesterol levels. Conclusions-Single intravenous AAV-PCSK9DY injection is a fast, easy, and cost-effective approach, resulting in rapid and long-term sustained hyperlipidemia and atherosclerosis. We demonstrate as a proof of concept the synergy between PCSK9 DY gain-of-function and ApoE deficiency. This methodology could allow testing of the genetic interaction of several mutations without the need for complex and time-consuming backcrosses.

show abstract

mentioning

confidence: 99%

Induction of Sustained Hypercholesterolemia by Single Adeno-Associated Virus–Mediated Gene Transfer of Mutant hPCSK9

Roche-Molina

Sanz-Rosa

Cruz

et al. 2015

ATVB

148

141

View full text Add to dashboard Cite

show abstract

“…To overcome this drawback of the adenoviral vector, AAV vectors have been developed [58]. AAV vectors are single-stranded, non-enveloped DNA viral vectors, 18–26 nm in diameter, with a genome of 4–5 kb [56,58,59]. AAV vectors can also transfect genes into both dividing and non-dividing cells, and may incorporate genes into the host genome.…”

Section: Viral and Non-viral Vectors For Renal Fibrosis In Vivomentioning

confidence: 99%

Nano-sized carriers in gene therapy for renal fibrosisin vivo

Miyazawa

Hirai

Ookawara

et al. 2017

Nano Reviews & Experiments

View full text Add to dashboard Cite

Renal fibrosis is the final common pathway leading to end-stage renal failure regardless of underlying initial nephropathies. No specific therapy has been established for renal fibrosis. Gene therapy is a promising strategy for the treatment of renal fibrosis. Nano-sized carriers including viral vectors and non-viral vectors have been shown to enhance the delivery and treatment effects of gene therapy for renal fibrosis in vivo. This review focuses on the mechanisms of renal fibrosis and the in vivo technologies and methodologies of nano-sized carriers in gene therapy for renal fibrosis. RESPONSIBLE EDITOR Alexander Seifalian Director of Nanotechnology & Regenerative Medicine Ltd., The London BioScience Innovation Centre, London, UNITED KINGDOM

show abstract

“…AAVs are single-stranded, non-enveloped DNA viral vectors 18–26 nm in diameter, with a genome of 4–5 kb [46,48,49]. AAVs can deliver transgenes into both dividing and non-dividing cells, and can incorporate their transgenes into the host genome [46,48,49].…”

Section: Nano-sized Carriers For Gene Therapy Of Peritoneal Fibrosismentioning

confidence: 99%

“…AAVs can deliver transgenes into both dividing and non-dividing cells, and can incorporate their transgenes into the host genome [46,48,49]. Intraperitoneal administration of AAVs expressing decorin significantly inhibited peritoneal fibrosis, associated with preserved peritoneal cell size, decreased peritoneal thickness, and decreased expression of α-SMA in the peritoneum in a mouse peritoneal fibrosis model [37].…”

Section: Nano-sized Carriers For Gene Therapy Of Peritoneal Fibrosismentioning

confidence: 99%

Nano-sized carriers in gene therapy for peritoneal fibrosisin vivo

Igarashi

Hoshino

Ookawara

et al. 2017

Nano Reviews & Experiments

View full text Add to dashboard Cite

Peritoneal fibrosis is a crucial complication in patients receiving peritoneal dialysis. It is a major pathological feature of peritoneal membrane failure, which leads to withdrawal of peritoneal dialysis. No specific therapy has yet been established for the treatment of peritoneal fibrosis. However, gene therapy may be a viable option, and various nano-sized carriers, including viral and non-viral vectors, have been shown to enhance the delivery and efficacy of gene therapy for peritoneal fibrosis in vivo. This review focuses on the use of nano-sized carriers in gene therapy of peritoneal fibrosis in vivo.

show abstract

Recombinant AAV as a Platform for Translating the Therapeutic Potential of RNA Interference

Cited by 119 publications

References 73 publications

Induction of Sustained Hypercholesterolemia by Single Adeno-Associated Virus–Mediated Gene Transfer of Mutant hPCSK9

Induction of Sustained Hypercholesterolemia by Single Adeno-Associated Virus–Mediated Gene Transfer of Mutant hPCSK9

Nano-sized carriers in gene therapy for renal fibrosisin vivo

Nano-sized carriers in gene therapy for peritoneal fibrosisin vivo

Contact Info

Product

Resources

About